Species-specific description:
The neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage diseases characterized by intraneuronal accumulation of fluorescent granules and early neuronal death. Affected Border collies present at 18-24 months of age. There is a genetic test available.

History:
This disorder in dogs was first reported by Taylor and Farrow (1988).

Mapping:
Melvile et al. (2005) genotyped animals in their pedigrees with microsatellites in "Likely candidate regions for the disease gene in Border collies based on the conserved synteny between the dog and the human genomes and the positions of NCL genes in human". Linkage analysis rejected chromosomes CFA6 and CFA37, but strongly implicated the region of CFA22 that is orthologous with the region of chromosome HSA13q21.1–q32 that contains CLN5, mutations in which give rise to this disorder in humans.

Molecular basis:
Sequencing of the strong comparative positional candidate gene CLN5 (see Mapping section above) revealed to Melville et al. (2005) that the causative mutation in Border Collies is "a nonsense mutation (Q206X) within exon 4" which "should result in a protein product of a size similar to that of some mutations identified in human CLN5 and therefore the Border collie may make a good model for human NCL". CLN5 encodes a soluble lysosomal glycoprotein, the function of which is unknown, but it interacts with the proteins of TPP1 and CLN3 (Vesa et al., 2002). Melville et al. (2005) report the causative variant as c.619C>T or p.Q206X. This curator (T.L.) thinks that the original protein designation (Melville et al. 2005) is incorrect and should actually read p.Q207X, based on the RefSeq entry NM_001011556.1 of the dog CLN 5 transcript.

Small deletion in Golden Retrievers: CLN5:c.934_935delAG; p.E312Vfs*6 (Gilliam et al., 2015), who explain that this mutation is "predicted to produce a frameshift and premature termination codon and encode a protein variant, CLN5:p.E312Vfs*6, which would lack 39 C-terminal amino acids".

Kolicheski et al. (2016) reported that affected Australian Cattle Dogs have the same causal mutation as reported by Melville et al. (2005) in Border Collies.